Recent advances in the role of MXene based hybrid architectures as electrocatalysts for water splitting.

The development of non-noble metal based and cost-effective electrocatalysts for water splitting has attracted significant attention due to their potential in production of clean and green hydrogen fuel. Discovered in 2011, a family of two-dimensional transition metal carbides, nitrides, and carbonitrides, have demonstrated promising performance as electro catalysts in the water splitting process due to their high electrical conductivity, very large surface area and abundant catalytic active sites. However, their-long term stability and recyclability are limited due to restacking and agglomeration of MXene flakes. This problem can be solved by combining MXene with other materials to create their hybrid architectures which have demonstrated higher electrocatalytic performance than pristine MXenes. Electrolysis of water encompasses two half-cell reactions, hydrogen evolution reaction (HER) at the cathode and oxygen evolution reaction (OER) at the anode. Firstly, this concise review explains the mechanism of water splitting. Then it provides an overview of the recent advances about applications of MXenes and their hybrid architectures as HER, OER and bifunctional electrocatalysts for overall water splitting. Finally, the recent challenges and potential outlook in the field have been presented. This concise review may provide further understanding about the role of MXene-based hybrid architectures to develop efficient electrocatalysts for water splitting.

Bioactivity and Metabolomics Profiling of Endophytic Actinobacteria Isolated from Roots of the Medicinal Plants Dominant in South Asian Region.

Background: Plant-derived endophytic actinobacteria are the center of attention due to their capacity to produce diverse antimicrobial and anticancer compounds and their metabolites influence plant growth. Methods: In this study, 40 endophytic actinobacteria strains were isolated from the roots of eight medicinal plants used as folk medicine in South Asian region. The isolates were characterized morphologically, biochemically and physiologically and the genus level identification of the selected strains was done by 16SrRNA gene sequencing. In small scale cultivation (50ml broth), the isolates were grown in A-medium to prepare the crude extracts. These crude extracts were subsequently evaluated for their antimicrobial, anticancer and antioxidant activity and the metabolomics profile of each of the extract was determined by TLC and HPLC-UV/MS. Results: The taxonomic studies showed that the isolates belong to the group actinobacteria based on their morphological and physiological characteristics and the 16SrRNA gene sequencing of the selected strains identified the genera including Streptomyces, Micromonospora and Nocardia. Cumulatively,53% of extracts exhibited anti-Gram-(+) activity,47% exhibited anti-Gram-(-) activity,32% exhibited antifungal activity and 30% were cytotoxic to PC3 and A549 cancer cell lines and most of the extracts have shown antioxidant activity greater than 50%. The metabolomics analysis predicted the presence of an array of low molecular weight metabolites and indicated the promising isolates in collection for further studies for novel bioactive metabolite isolation and structure elucidation. Conclusion: Overall the study provides an overview of the endophytic actinobacteria residing in the roots of the selected medicinal plants prevalent in south Asian region and their potential to produce the medicinally and biotechnologically useful compounds.

Prevalence and antibiotics resistance status of Salmonella in raw meat consumed in various areas of Lahore, Pakistan.

This study reports the prevalence and antibiotics resistance status of Salmonella detected in raw meat from Lahore, Pakistan. Overall, N = 111 meat samples, were collected from local markets. Salmonella was recovered from 57 (51.35%) samples, including 45.83% of poultry, 60% of buffalo, 64.28% of cow, and 60% of goat meat samples. The predominant Salmonella strains were Salmonella enterica serovars; Typhimurium (45.4%), Typhi (27.2%), and Enteritidis (18.1%), identified by VITEK system and 16S rRNA gene sequencing. The isolates exhibited high resistance to Erythromycin (100%), Cefepime (98.24%), Colistin (94.73%), Azithromycin (92.98%), Tetracycline (87.71%), Polymyxin B (84.21%), Ciprofloxacin (84.21%), Trimethoprim-Sulfamethoxazole (80.70%), Nalidixic Acid (80.70%), Kanamycin (78.94%), Chloramphenicol (77.19%), Streptomycin (71.92%) and Ampicillin (64.91%). While the isolates exhibited more susceptibility to Meropenem (75.43%) and Amikacin (73.68%). N = 8 strains were designated as Multidrug Resistant (MDR) and N = 3 as Extensively Drug-Resistant (XDR) Salmonella. The PCR-based detection of resistance genes revealed the presence of blaTEM-1 gene (100%), catA1 gene (64%), and gyrA gene (18%). The whole genome sequencing (WGS) of two selected strains and subsequent downstream analysis confirmed the strains as MDR and XDR Salmonella enterica serovar Typhi. The study showed that raw meat consumed in Lahore carries a significantly high number of drug-resistant Salmonella.

Fatty acid based antimicrobials from Streptomyces sp. SORS-24, an endophyte isolated from Sonchus oleraceus.

Due to the rise in bacterial resistance towards various therapeutic agents, interest is now developing towards fatty acid based antimicrobials because of their non-specific mode of action. A strain SORS 24 isolated from Sonchus oleraceus (Sow thistle) showed significant activity against Escherichia coli ATCC 25922 (25 mm), Chlorella vulgaris (20 mm), Bacillus subtilis DSM 10 (ATCC 6051) and Pseudomonas sp. (15 mm). It displayed an LC50 value of 10 µg/ml against Artemia salina (Brine shrimp) nauplii and an EC50 value of 0.8 µg/ml in the (DPPH) diphenylpicrylhydrazyl antioxidant assay. The strain also displayed genotoxicity against a PolA deficient strain, E. coli K-12 AB 3027 (15 mm). Mass spectrometry (HPLC-MS) showed that the strain produced oleamide (9-Octadecenamide) and erucamide (13-Docosenamide). Both of the purified fatty acid amides showed prominent activity against B. subtilis DSM 10 (ATCC 6051) (20 mm) and E. coli ATCC 25922 (15 mm). Significant genotoxicity was observed against E. coli K-12 AB 3027 (15 mm). The 16S gene sequencing revealed that the strain belonged to species, Streptomyces tanashiensis. As far as our understanding, this is the first report of this species producing these fatty acid based antimicrobials.

Bioprospecting of desert actinobacteria with special emphases on griseoviridin, mitomycin C and a new bacterial metabolite producing Streptomyces sp. PU-KB10-4.

BACKGROUND: Bioprospecting of actinobacteria isolated from Kubuqi desert, China for antibacterial, antifungal and cytotoxic metabolites production and their structure elucidation. RESULTS: A total of 100 actinobacteria strains were selectively isolated from Kubuqi desert, Inner Mongolia, China. The taxonomic characterization revealed Streptomyces as the predominant genus comprising 37 different species, along with the rare actinobacterial genus Lentzea. The methanolic extracts of 60.8% of strains exhibited potent antimicrobial activities against Staphylococcus aureus, Micrococcus luteus, Bacillus subtilis, Escherichia coli, Salmonella enterica, Saccharomyces cerevisiae and high to mild in vitro cytotoxicity against PC3 (prostate cancer) and A549 (lung carcinoma) cell lines. The metabolomics analysis by TLC, HPLC-UV/vis, HPLC-MS and NMR showed the presence of compounds with molecular weights ranging from 100 to 1000 Da. The scale-up fermentation of the prioritized anti-Gram-negative strain PU-KB10-4 (Streptomyces griseoviridis), yielded three pure compounds including; griseoviridin (1; 42.0 mgL- 1) with 20 fold increased production as compared to previous reports and its crystal structure as monohydrate form is herein reported for the first time, mitomycin C (2; 0.3 mgL- 1) and a new bacterial metabolite 4-hydroxycinnamide (3; 0.59 mgL- 1). CONCLUSIONS: This is the first report of the bioprospecting and exploration of actinobacteria from Kubuqi desert and the metabolite 4-hydroxycinnamide (3) is first time isolated from a bacterial source. This study demonstrated that actinobacteria from Kubuqi desert are a potential source of novel bioactive natural products. Underexplored harsh environments like the Kubuqi desert may harbor a wider diversity of actinobacteria, particularly Streptomyces, which produce unique metabolites and are an intriguing source to develop medicinally valuable natural products.

Morphogenetic variation and assorted biological activities in true branching Nostocales strains of Cholistan oasis, Pakistan.

From the oasis of Cholistan, true branching heterocystous cyanobacterial strains were studied for, the cell arrangement in primary branches being mono- or bi-seriate; the shape of cells in main filament large and irregular; profused secondary branching emerging on one or both sides and tapering along their length. In these observed traits, two clear morphological taxa were recognized, both well-assorted from the previously described species of the genus Westiellopsis. Both strains showed culturing responses and were studied for antibacterial, cytotoxic, and anticancer potentials. The strain derived from the site B-10 provenance exhibited antibacterial activity against Pseudomonas (18 mm), Klebsiella (15 mm), Staphylococcus (22 mm). On the contrary, the strain of site A-44 showed no activity against any of the above-mentioned bacterial strains. The cytotoxicity assay for the strain of the B-10 site showed 36% larval mortality, whereas strain A-44 showed 24% larval mortality. Performance of the strain B-10 in MTT assay (assessed on HCT-116 cell lines) revealed a dose-dependent activity: at 200, 100, 50, and 25 µg/ml; achieving a growth inhibition of 50.15%, 40.22%, 33.72%, and 10.21%, respectively; and the strain of A-44 could only exhibit a 30.06% growth inhibition at 200 µg/ml. The 16S rRNA sequencing revealed the sequence homology with Neowestiellopsis. Based on data presented here we report two diverse taxa of true branching Nostocales from Cholistan oasis, Pakistan.

Cytotoxic Evaluation and Molecular Docking Studies of Aminopyridine Derivatives as Potential Anticancer Agents.

BACKGROUND: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate for this therapeutic failure. OBJECTIVES: The current study demonstrated whether N-protected and deprotected amino acid derivatives of 2- aminopyridine could attenuate tumor development using colorectal cancer cell lines. METHODS: Biological assays were performed to investigate the anticancer potential of synthesized compounds. The in silico ADME profiling and docking studies were also performed by docking the designed compounds against the active binding site of beta-catenin (CTNNB1) to analyze the binding mode of these compounds. Four derivatives 4a, 4b, 4c, and 4d were selected for investigation of in vitro anticancer potential using colorectal cancer cell line HCT 116. The anti-tumor activities of synthesized compounds were further validated by evaluating the inhibitory effects of these compounds on the target protein beta-catenin through in vitro enzyme inhibitory assay. RESULTS: The docking analysis revealed favorable binding energies and interactions with the target proteins. The in vitro MTT assay on colorectal cancer cell line HCT 116 and HT29 revealed potential anti-tumor activities with an IC50 range of 3.7-8.1µM and 3.27-7.7 µM, respectively. The inhibitory properties of these compounds on the concentration of beta-catenin by ELISA revealed significant percent inhibition of target protein at 100 µg/ml. CONCLUSION: In conclusion, the synthesized compounds showed significant anti-tumor activities both in silico and in vitro, having potential for further investigating its role in colorectal cancer.

'Diagnostic downshift': clinical and system consequences of extrapolating secondary care testing tactics to primary care.

Numerous drivers push specialist diagnostic approaches down to primary care ('diagnostic downshift'), intuitively welcomed by clinicians and patients. However, primary care's different population and processes result in under-recognised, unintended consequences. Testing performs poorer in primary care, with indication creep due to earlier, more undifferentiated presentation and reduced accuracy due to spectrum bias and the 'false-positive paradox'. In low-prevalence settings, tests without near-100% specificity have their useful yield eclipsed by greater incidental or false-positive findings. Ensuing cascades and multiplier effects can generate clinician workload, patient anxiety, further low-value tests, referrals, treatments and a potentially nocebic population 'disease' burden of unclear benefit. Increased diagnostics earlier in pathways can burden patients and stretch general practice (GP) workloads, inducing downstream service utilisation and unintended 'market failure' effects. Evidence is tenuous for reducing secondary care referrals, providing patient reassurance or meaningfully improving clinical outcomes. Subsequently, inflated investment in per capita testing, at a lower level in a healthcare system, may deliver diminishing or even negative economic returns. Test cost poorly represents 'value', neglecting under-recognised downstream consequences, which must be balanced against therapeutic yield. With lower positive predictive values, more tests are required per true diagnosis and cost-effectiveness is rarely robust. With fixed secondary care capacity, novel primary care testing is an added cost pressure, rarely reducing hospital activity. GP testing strategies require real-world evaluation, in primary care populations, of all downstream consequences. Test formularies should be scrutinised in view of the setting of care, with interventions to focus rational testing towards those with higher pretest probabilities, while improving interpretation and communication of results.

Unintended consequences: quantifying the benefits, iatrogenic harms and downstream cascade costs of musculoskeletal MRI in UK primary care.

OBJECTIVES: The largest proportion of general practitioner (GP) magnetic resonance imaging (MRI) is musculoskeletal (MSK), with consistent annual growth. With limited supporting evidence and potential harms from early imaging overuse, we evaluated practice to improve pathways and patient safety. METHODS: Cohort evaluation of routinely collected diagnostic and general practice data across a UK metropolitan primary care population. We reviewed patient characteristics, results and healthcare utilisation. RESULTS: Of 306 MSK-MRIs requested by 107 clinicians across 29 practices, only 4.9% (95% CI ±2.4%) appeared clearly indicated and only 16.0% (95% CI ±4.1%) received appropriate prior therapy. 37.0% (95% CI ±5.5%) documented patient imaging request. Most had chronic symptoms and half had psychosocial flags. Mental health was addressed in only 11.8% (95% CI ±6.3%) of chronic sufferers with psychiatric illness, suggesting a solely pathoanatomical approach to MSK care. Only 7.8% (95% CI ±3.0%) of all patients were appropriately managed without additional referral. 1.3% (95% CI ±1.3%) of scans revealed diagnoses leading to change in treatment (therapeutic yield). Most imaged patients received pathoanatomical explanations to their symptoms, often based on expected age or activity-related changes. Only 16.7% (95% CI ±4.2%) of results appeared correctly interpreted by GPs, with spurious overperception of surgical targets in 65.4% (95% CI ±5.3%) who suffered 'low-value' (ineffective, harmful or wasteful) post-MRI referral cascades due to misdiagnosis and overdiagnosis. Typically, 20%-30% of GP specialist referrals convert to a procedure, whereas MRI-triggered referrals showed near-zero conversion rate. Imaged patients experienced considerable delay to appropriate care. Cascade costs exceeded direct-MRI costs and GP-MSK-MRI potentially more than doubles expenditure compared with physiotherapist-led assessment services, for little-to-no added therapeutic yield, unjustifiable by cost-consequence or cost-utility analysis. CONCLUSION: Unfettered GP-MSK-MRI use has reached unaccceptable indication creep and disutility. Considerable avoidable harm occurs through ubiquitous misinterpretation and salient low-value referral cascades for two-thirds of imaged patients, for almost no change in treatment. Any marginally earlier procedural intervention for a tiny fraction of patients is eclipsed by negative consequences for the vast majority. Only 1-2 patients need to be scanned for one to suffer mismanagement. Direct-access imaging is neither clinically, nor cost-effective and deimplementation could be considered in this setting. GP-MSK-MRI fuels unnecessary healthcare utilisation, generating nocebic patient beliefs and expectations, whilst appropriate care is delayed and a high burden of psychosocial barriers to recovery appear neglected.

Taxonomic and Metabolomics Profiling of Actinobacteria Strains from Himalayan Collection Sites in Pakistan.

Actinobacteria have proven themselves as the major producers of bioactive compounds with wide applications. In this study, 35 actinobacteria strains were isolated from soil samples collected from the Himalayan mountains region in Pakistan. The isolated strains were identified by polyphasic taxonomy and were prioritized based on biological and chemical screening to identify the strains with ability to produce inimitable metabolites. The biological screening included antimicrobial activity against Staphylococcus aureus, Micrococcus luteus, Salmonella enterica, Escherichia coli, Mycobacterium aurum, and Bacillus subtilis and anticancer activity using human cancer cell lines PC3 and A549. For chemical screening, methanolic extracts were investigated using TLC, HPLC-UV/MS. The actinobacteria strain PU-MM93 was selected for scale-up fermentation based on its unique chemical profile and cytotoxicity (50-60% growth inhibition) against PC3 and A549 cell lines. The scale-up fermentation of PU-MM93, followed by purification and structure elucidation of compounds revealed this strain as a promising producer of the cytotoxic anthracycline aranciamycin and aglycone SM-173-B along with the potent neuroprotective carboxamide oxachelin C. Other interesting metabolites produced include taurocholic acid as first report herein from microbial origin, pactamycate and cyclo(L-Pro-L-Leu). The study suggested exploring more bioactive microorganisms from the untapped Himalayan region in Pakistan, which can produce commercially significant compounds.

Himalaquinones A-G, Angucyclinone-Derived Metabolites Produced by the Himalayan Isolate Streptomyces sp. PU-MM59.

Himalaquinones A-G, seven new anthraquinone-derived metabolites, were obtained from the Himalayan-based Streptomyces sp. PU-MM59. The chemical structures of the new compounds were identified based on cumulative analyses of HRESIMS and NMR spectra. Himalaquinones A-F were determined to be unique anthraquinones that contained unusual C-4a 3-methylbut-3-enoic acid aromatic substitutions, while himalaquinone G was identified as a new 5,6-dihydrodiol-bearing angucyclinone. Comparative bioactivity assessment (antimicrobial, cancer cell line cytotoxicity, impact on 4E-BP1 phosphorylation, and effect on axolotl embryo tail regeneration) revealed cytotoxic landomycin and saquayamycin analogues to inhibit 4E-BP1p and inhibit regeneration. In contrast, himalaquinone G, while also cytotoxic and a regeneration inhibitor, did not affect 4E-BP1p status at the doses tested. As such, this work implicates a unique mechanism for himalaquinone G and possibly other 5,6-dihydrodiol-bearing angucyclinones.

Motilibacter deserti sp. nov. and Motilibacter aurantiacus sp. nov., two novel actinobacteria isolated from soil of Cholistan Desert and emended description of the genus Motilibacter.

Two novel actinobacterial strains, designated as E257T and K478T, were isolated from hyper-arid soil samples collected in Cholistan Desert, Pakistan. Comparative analysis of 16S rRNA genes showed that strains E257T and K478T were assigned to the genus Motilibacter, being their closest relative M. rhizosphaerae RS-16T with 97.3% and 96.7% similarities, respectively. The sequence similarity between strain E257T and K478T was 98.9%. Phylogenetic analysis based on 16S rRNA gene sequences and phylogenomic analysis based on multiple genes of conserved core proteins exhibited that these two strains belonged to the genus Motilibacter and formed a robust cluster separated from the two type species of the genus Motilibacter. Average Nucleotide Identity (ANI), Average Amino acid Identity (AAI), digital DNA-DNA hybridization (dDDH) values and Percentage of Conserved Proteins (POCP) calculated from the complete genome sequences indicated strains E257T and K478T were assigned into genus Motilibacter but clearly separated from each other and from the other species of the genus Motilibacter with values below the thresholds for species delineation. The two isolates were found to have chemotaxonomic, cultural and morphological properties consistent with their classification in the genus Motilibacter and also confirmed the differentiation from their closest species. The obtained results demonstrated that strains E257T and K478T represent two novel species of the genus Motilibacter, for which the names Motilibacter desertisp. nov. (type strain E257T = JCM 33651T = CGMCC 1.17159T) and Motilibacter aurantiacus sp. nov. (type strain K478T =JCM 33652T =CGMCC 1.17229T) are proposed.

Arthrobacter mobilis sp. nov., a novel actinobacterium isolated from Cholistan desert soil.

A Gram-stain-positive, aerobic, catalase-positive, oxidase-negative, non-mycelium-forming, motile, rod-shaped with one polar flagellum actinobacterium, designated E918T, was isolated from a desert soil collected in Cholistan desert, Pakistan. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain E918T belonged to the genus Arthrobacter and was most closely related to Arthrobacter deserti CGMCC 1.15091T (97.2 % similarity). The peptidoglycan was of the A3α type and the whole-cell sugar profile was found to contain galactose. The major menaquinone was MK-9(H2). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and two unidentified glycolipids. The major fatty acids identified were anteiso-C15 : 0 and anteiso-C17 : 0. The G+C content of the genomic DNA was 68.69 mol%. The digital DNA-DNA hybridization and average nucleotide identity values between strain E918T and A. deserti CGMCC 1.15091T were 28.0 and 83.4%, respectively. On the basis of its phylogenetic, phenotypic and chemotaxonomic features, strain E918T was considered to represent a novel species of the genus Arthrobacter, for which the name Arthrobacter mobilis sp. nov. is proposed. The type strain of Arthrobacter mobilis is E918T (=JCM 33392T=CGMCC 1.16978T).

PCR-based Screening Approach: A Rapid Method to Detect the Biosynthetic Potential of Antimicrobials in Actinobacterial Strains.

This study aimed to investigate the PCR-based screening strategy for the prediction of the antimicrobial biosynthetic potential of the selected Streptomyces strains originated from an extreme environment (Cholistan Desert, Pakistan). The biosynthetic potential was determined by using both molecular and culture-dependent screening approaches. The four biosynthetic genes clusters, including the pks-1, nrps, cyp P450 hydroxylase (cyps), and glycopeptide oxy b genes, were investigated in the selected strains by PCR amplification, sequencing, and by subsequent bioinformatics approaches. Among the 40 selected Streptomyces strains, 33 strains possessed the nrps gene, 17 strains carried the pks-1 gene, four strains were found to have the cyps gene, and none of the strain carried oxy b gene. The Streptomyces strains including NR-1, NR-10, NR-14, and NR-15 were investigated for in vitro antifungal activity against Fusarium oxysporum, Rhizoctonia solani, and Aspergillus sp. The extracts were analyzed for chemical profiling (TLC and HPLC-UV), and a unique pattern of secondary metabolites was observed. The selected strains exhibited pronounced antifungal activity against the fungal test strains with the zone of inhibition up to 17, 18, and 19 mm, respectively. The study depicts that gene-based screening can be successfully applied to identify potentially bioactive strains by usin a single screening process. This PCR-based approach is rapid and can be used for sorting out and selecting the potential candidate among actinobacterial culture collections. Such a preselection or strain prioritization consequently decreases the time and efforts required for selecting the potential bioactive strain, which then can be subjected to the detailed chemical analysis.This study aimed to investigate the PCR-based screening strategy for the prediction of the antimicrobial biosynthetic potential of the selected Streptomyces strains originated from an extreme environment (Cholistan Desert, Pakistan). The biosynthetic potential was determined by using both molecular and culture-dependent screening approaches. The four biosynthetic genes clusters, including the pks-1, nrps, cyp P450 hydroxylase (cyps), and glycopeptide oxy b genes, were investigated in the selected strains by PCR amplification, sequencing, and by subsequent bioinformatics approaches. Among the 40 selected Streptomyces strains, 33 strains possessed the nrps gene, 17 strains carried the pks-1 gene, four strains were found to have the cyps gene, and none of the strain carried oxy b gene. The Streptomyces strains including NR-1, NR-10, NR-14, and NR-15 were investigated for in vitro antifungal activity against Fusarium oxysporum, Rhizoctonia solani, and Aspergillus sp. The extracts were analyzed for chemical profiling (TLC and HPLC-UV), and a unique pattern of secondary metabolites was observed. The selected strains exhibited pronounced antifungal activity against the fungal test strains with the zone of inhibition up to 17, 18, and 19 mm, respectively. The study depicts that gene-based screening can be successfully applied to identify potentially bioactive strains by usin a single screening process. This PCR-based approach is rapid and can be used for sorting out and selecting the potential candidate among actinobacterial culture collections. Such a preselection or strain prioritization consequently decreases the time and efforts required for selecting the potential bioactive strain, which then can be subjected to the detailed chemical analysis.

Auraticoccus cholistanensis sp. nov., an actinomycete isolated from soil of the Cholistan Desert, and emended description of the genus Auraticoccus.

A Gram-stain-positive, aerobic, non-motile and non-spore-forming actinobacterium, designated as F435T, was isolated from soil sample collected from the Cholistan Desert, Pakistan. The taxonomic position of the strain was established by using a polyphasic taxonomic approach. The cells were coccoid-shaped and found in single or arrangement of pairs. The novel strain grew at 15‒37 °C (optimum, 25‒30 °C), pH 7‒11 (optimum, pH 7-8) and in the presence of 0‒8% (w/v) NaCl (optimum, 0 %). Results of blast analysis based on 16S rRNA gene sequences showed that Auraticoccus monumenti MON 2.2T was its closest relative with 97.4 % similarity followed by Desertihabitans aurantiacus CPCC 204711T (95.2 %). In phylogenetic trees, strain F435T formed a robust cluster with the only member of the genus Auraticoccus. The peptidoglycan isomer present in the cell wall was ll-diaminopimelic acid. The major fatty acid was determined to be anteiso-C15 : 0. Characteristic polar lipids of the strain were diphosphatidylglycerol, phosphatidylglycerol, phosphoglycolipids and glycolipids. The predominant menaquinone was MK-9(H4). The genomic G+C content was calculated as 73.5 mol%. The digital DNA-DNA hybridization (GGDC) and average nucleotide identity (ANI) values between strain F435T and A. monumenti MON 2.2T were 24.6 and 81.8 %, respectively. Based on the results of phenotypic, chemotaxonomic, phylogenetic and phylogenomic analyses, strain F435T represents a novel specie of the genus Auraticoccus, for which the name Auraticoccus cholistanensis sp. nov. is proposed. The type strain is F435T (=JCM 33648T=CGMCC 1.17443T). The description of the genus Auraticoccus has also been emended.

Ethics education and moral decision-making in clinical commissioning: an interview study.

BACKGROUND: Clinical commissioning involves ethically challenging decisions about health resource allocation. However, commissioners come from a range of professional backgrounds with varying levels of training and expertise in ethical decision-making. Hence, they may lack the relevant training and resources to feel fully prepared for this increasingly demanding role. AIM: This study aims to provide insight into how prepared commissioners feel in making ethical decisions; what ethics learning needs they might have; and how these might be addressed. DESIGN AND SETTING: This qualitative interview study explored the experiences of commissioners working for clinical commissioning groups (CCGs) in England. METHOD: Eighteen participants were interviewed between December 2017 and July 2018 using a purposive sampling approach to participant selection. Transcriptions were coded and analysed using the constant comparative method of thematic analysis. RESULTS: Most participants had not received ethics training in preparation for, or during, their commissioning role, and reported difficulties identifying and analysing ethical issues. Participants often felt uncomfortable about decisions they were involved in, attributing this to a number of factors: a sense of moral unease; concerns that CCGs' decision-making processes were not sufficiently transparent; and that CCGs were not fully accountable to the population served. CONCLUSION: Commissioners face complex decisions involving ethical issues, and associated moral unease is exacerbated by a lack of ethics training and lack of confidence in identifying and analysing these. This study shows a clear need for additional support and ethics training for commissioners to support them in this area of decision-making.

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents.

This study reports the formation of 5-FU co-crystals with four different pharmacologically safe co-formers; Urea, Thiourea, Acetanilide and Aspirin using methanol as a solvent. Two fabrication schemes were followed i.e., solid-state grinding protocol, in which API and co-formers were mixed through vigorous grinding while in the other method separate solutions of both the components were made and mixed together. The adopted approaches offer easy fabrication protocols, no temperature maintenance requirements, no need of expensive solvents, hardly available apparatus, isolation and purification of the desired products. In addition, there is no byproducts formation, In fact, a phenomenon embracing the requirements of green synthesis. Through FTIR analysis; for API the N-H absorption frequency was recorded at 3409.02 cm-1 and that of -C[bond, double bond]O was observed at 1647.77 cm-1. These characteristics peaks of 5-FU were significantly shifted and recorded at 3499.40 cm-1 and 1649.62 cm-1 for 5-FU-Ac (3B) and 3496.39 cm-1 and 1659.30 cm-1 for 5-FU-As (4B) co-crystals for N-H and -C[bond, double bond]O groups respectively. The structural differences between API and co-crystals were further confirmed through PXRD analysis. The characteristic peak of 5-FU at 2θ = 28.79918o was significantly shifted in the graphs of co-crystals not only in position but also with respect to intensity and FWHM values. In addition, new peaks were also recorded in all the spectra of co-formers confirming the structural differences between API and co-formers. In addition, percent growth inhibition was also observed by all the co-crystals through MTT assay against HCT 116 colorectal cell lines in vitro. At four different concentrations; 25, 50, 100 and 200 µg/mL, slightly different trends of the effectiveness of API and co-crystals were observed. However; among all the co-crystal forms, 5-FU-thiourea co-crystals obtained through solution method (2B) proved to be the most effective growth inhibitor at all the four above mentioned concentrations.

Synthesis and characterization of silver nanoparticle-decorated cobalt nanocomposites (Co@AgNPs) and their density-dependent antibacterial activity.

Magnetic cores loaded with metallic nanoparticles can be promising nano-carriers for successful drug delivery at infectious sites. We report fabrication, characteristic analysis and in vitro antibacterial performance of nanocomposites comprising cobalt cores (Co-cores) functionalized with a varied concentration of silver nanoparticles (AgNPs). A two-step polyol process synchronized with the transmetalation reduction method was used. Co-cores were synthesized with cobalt acetate, and decoration of AgNPs was carried out with silver acetate. The density of AgNPs was varied by changing the amount of silver content as 0.01, 0.1 and 0.2 g in the synthesis solution. Both AgNPs and Co-cores were spherical having a size range of 30-80 nm and 200 nm to more than 1 µm, respectively, as determined by scanning electron microscopy. The metallic nature and face-centred cubic crystalline phase of prepared nanocomposites were confirmed by X-ray diffraction. Biocompatibility analysis confirmed high cell viability of MCF7 at low concentrations of tested particles. The antibacterial performance of nanocomposites (Co@AgNPs) against Escherichia coli and Bacillus subtilis was found to be AgNPs density-dependent, and nanocomposites with the highest AgNPs density exhibited the maximum bactericidal efficacy. We therefore propose that Co@AgNPs as effective drug containers for various biomedical applications.

Baraphenazines A-G, Divergent Fused Phenazine-Based Metabolites from a Himalayan Streptomyces.

The structures and bioactivities of three unprecedented fused 5-hydroxyquinoxaline/alpha-keto acid amino acid metabolites (baraphenazines A-C, 1-3), two unique diastaphenazine-type metabolites (baraphenazines D and E, 4 and 5) and two new phenazinolin-type (baraphenazines F and G, 6 and 7) metabolites from the Himalayan isolate Streptomyces sp. PU-10A are reported. This study highlights the first reported bacterial strain capable of producing diastaphenazine-type, phenazinolin-type, and izumiphenazine A-type metabolites and presents a unique opportunity for the future biosynthetic interrogation of late-stage phenazine-based metabolite maturation.